Evidence map›Paper›PMID 33157009›Full record

ArticleAmerican journal of human genetics2020

NCKAP1 Disruptive Variants Lead to a Neurodevelopmental Disorder with Core Features of Autism.

Hui Guo, Qiumeng Zhang, Rujia Dai, Bin Yu, Kendra Hoekzema, Jieqiong Tan, Senwei Tan, Xiangbin Jia, Wendy K Chung, Rebecca Hernan and 48 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 40 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

58 authors at 20 institutions in 8 countries.

Hui GuoCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address: guohui@sklmg.edu.cn.
Qiumeng ZhangCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
Rujia DaiCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Bin YuCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
Kendra HoekzemaDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Jieqiong TanCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
Senwei TanCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
Xiangbin JiaCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
Wendy K ChungDepartment of Pediatrics and Medicine, Columbia University, New York, NY 10027, USA.
Rebecca HernanDepartment of Pediatrics and Medicine, Columbia University, New York, NY 10027, USA.
Fowzan S AlkurayaDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
Ahood AlsulaimanDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
Mohammad A Al-MuhaizeaDepartment of Neurosciences, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
Gaetan LescaDepartment of Medical Genetics, Lyon University Hospital, Lyon 69000, France.
Linda PonsDepartment of Medical Genetics, Lyon University Hospital, Lyon 69000, France.
Audrey LabalmeDepartment of Medical Genetics, Lyon University Hospital, Lyon 69000, France.
Linda LauxAnn & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
Emily BryantAnn & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
Natasha J BrownDepartment of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3010, Australia; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.
Elena SavvaDepartment of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, VIC 3010, Australia.
Samantha AyresVictorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia; Melbourne Genomics Health Alliance, Melbourne, VIC 3010, Australia.
Dhamidhu EratneMelbourne Genomics Health Alliance, Melbourne, VIC 3010, Australia; Neuropsychiatry, Royal Melbourne Hospital, Melbourne, VIC 3010, Australia.
Hilde PeetersCentre for Human Genetics, KU Leuven and Leuven Autism Research (LAuRes), Leuven 3000, Belgium.
Frédéric BilanService de Génétique, CHU de Poitiers, Poitiers 86000, France.
Lucile Letienne-CejudoService de Génétique, CHU de Poitiers, Poitiers 86000, France.
Brigitte Gilbert-DussardierService de Génétique, CHU de Poitiers, Poitiers 86000, France.
Inge-Lore Ruiz-AranaService of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne 1011, Switzerland.
Jenny Meylan MerliniService of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne 1011, Switzerland.
Alexia BoizotService of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne 1011, Switzerland.
Lucia BartoloniService of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne 1011, Switzerland.
Federico SantoniService of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne 1011, Switzerland; Faculty of Biology and Medicine, University of Lausanne, Lausanne 1005, Switzerland.
Danielle KarlowiczDivision of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
Marie McDonaldDivision of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
Huidan WuCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
Zhengmao HuCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
Guodong ChenCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
Jianjun OuMental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.
Charlotte Brasch-AndersenDepartment of Clinical Genetics, Odense University Hospital, Odense 5000, Denmark.
Christina R FagerbergDepartment of Clinical Genetics, Odense University Hospital, Odense 5000, Denmark.
Inken DreyerDepartment of Pediatrics, Hospital Sønderjylland, Aabenraa 6200, Denmark.
Anne Chun-Hui TsaiDepartment of Pediatrics/Section of Genetics, University of Oklahoma Health Sciences Center, Oklahoma, OK 73019, USA; Section of Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO 80045, USA.
Valerie SlegeskySection of Genetics and Metabolism, Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO 80045, USA.
Rose B McGeeDivision of Cancer Predisposition, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Brina DanielsSection of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR 72701, USA.
Elizabeth A SellarsSection of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR 72701, USA.
Lori A CarpenterSaint Francis Health System, Inc. St Francis Health Systems, Tulsa, OK 74101, USA.
Bradley SchaeferArkansas Children's Hospital, Little Rock, AR 72202, USA.
Maria J Guillen SacotoGeneDx, Gaithersburg, MD 20877, USA.
Amber BegtrupGeneDx, Gaithersburg, MD 20877, USA.
Rhonda E SchnurGeneDx, Gaithersburg, MD 20877, USA.
Sumit PunjGeneDx, Gaithersburg, MD 20877, USA.
Ingrid M WentzensenGeneDx, Gaithersburg, MD 20877, USA.
Lindsay RhodesGeneDx, Gaithersburg, MD 20877, USA.
Qian PanCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
Raphael A BernierDepartment of Psychiatry, University of Washington, Seattle, WA 98195, USA.
Chao ChenCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
Evan E EichlerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Kun XiaCenter for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China; Hunan Key Laboratory of Animal Models for Human Diseases, Changsha, Hunan 410078, China; CAS Center for Excellence in Brain Science and Intelligences Technology (CEBSIT), Chinese Academy of Sciences, Shanghai 200000, China. Electronic address: xiakun@sklmg.edu.cn.
Central South University · CNUniversity of Lausanne · CHCentre Hospitalier Universitaire de Poitiers · FRHospices Civils de Lyon · FRKing Faisal Specialist Hospital & Research Centre · SAUniversity of Washington · USColumbia University · USDuke Medical Center · USLurie Children's Hospital · USOdense University Hospital · DKUniversity of Arkansas for Medical Sciences · USUniversity of Melbourne · AUArkansas Children's Hospital · USChildren's Hospital Colorado · USChinese Academy of Sciences · CNKU Leuven · BEMelbourne Genomics Health Alliance · AUSaint Francis Health System · USSt. Jude Children's Research Hospital · USSUNY Upstate Medical University · US

Funding

Mechanisms of Brain Dysmorphology in MN1 C-Terminal Truncation Syndrome, a Novel Intellectual Developmental Disability Disorder P50HD103524 · NICHD · UNIVERSITY OF WASHINGTON · PI DANIEL DOHERTY · 2020 to 2026
$9.9M
Sporadic Mutations and Autism Spectrum DisordersR01MH101221 · NIMH · UNIVERSITY OF WASHINGTON · PI EICHLER, EVAN · 2013 to 2025
$9.2M
NICHD NIH HHS P50 HD103524NIMH NIH HHS R01 MH101221
6 · The paper itself

Abstract

NCKAP1/NAP1 regulates neuronal cytoskeletal dynamics and is essential for neuronal differentiation in the developing brain. Deleterious variants in NCKAP1 have been identified in individuals with autism spectrum disorder (ASD) and intellectual disability; however, its clinical significance remains unclear. To determine its significance, we assemble genotype and phenotype data for 21 affected individuals from 20 unrelated families with predicted deleterious variants in NCKAP1. This includes 16 individuals with de novo (n = 8), transmitted (n = 6), or inheritance unknown (n = 2) truncating variants, two individuals with structural variants, and three with potentially disruptive de novo missense variants. We report a de novo and ultra-rare deleterious variant burden of NCKAP1 in individuals with neurodevelopmental disorders which needs further replication. ASD or autistic features, language and motor delay, and variable expression of intellectual or learning disability are common clinical features. Among inherited cases, there is evidence of deleterious variants segregating with neuropsychiatric disorders. Based on available human brain transcriptomic data, we show that NCKAP1 is broadly and highly expressed in both prenatal and postnatal periods and demostrate enriched expression in excitatory neurons and radial glias but depleted expression in inhibitory neurons. Mouse in utero electroporation experiments reveal that Nckap1 loss of function promotes neuronal migration during early cortical development. Combined, these data support a role for disruptive NCKAP1 variants in neurodevelopmental delay/autism, possibly by interfering with neuronal migration early in cortical development.

Indexed as

MutationAdaptor Proteins, Signal TransducingAdolescentAnimalsAutism Spectrum DisorderCerebral CortexChildFemaleGene ExpressionGenotypeHEK293 CellsHumansIntellectual DisabilityLearning DisabilitiesMaleMiceAdaptor Proteins, Signal TransducingNCKAP1 protein, humanProtein IsoformsRNA, Small Interferingautism spectrum disorderde novo variantsdisruptive variantgenotype-phenotype correlationNCKAP1neurodevelopmental disorder

Identifiers

PMID33157009
PMCPMC7674997
OpenAlexW3097947115

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.